The etiology of acute renal failure is undoubtedly multifactoral but the role of tubular transport defects in this syndrome has never been adequately studied. There are several experimental models of acute renal failure induced by neprotoxins or ischemia which have been explored using micropuncture and clearance methodology. The proposed research will attempt to define the segment specific tubular transport defects in various models of acute renal failure by means of isolated tubule microperfusion and evaluate the ability of current and proposed modalities to ameliorate or reverse these defects. Acute renal failure will be induced in rabbits by a) renal artery occlusion (60 min and 30 min), b) glycerol injection and c) uranyl nitrate. In each model the function of the proximal convoluted tubule and, the proximal straight tubule, will be assessed by measurement of the potential difference and fluid reabsorptive capacity. In addition, the ability of small molecules to permeate the tubule will be assessed by 14C labelled sucrose. The function of the thick ascending limb of Henle's loop will be assessed in each model by measurement of diluting ability and capacity to lower the chloride on concentration of the perfusate. In addition the Cl- and Na plus permeabilities will be investigated by use of 36Cl and 22Na isotopes, the function of the cortical collecting tubule will be evaluated by determination of net sodium and potassium transport and by the ability to respond to a maximal ADH stimulus. After the transport alterations are identified in each model, various methods will be explored to reverse or ameliorate these defects. The protective modalities include a) mannitol diuresis b) lasix diuresis, c) propranolol infusion, d) cyclic-AMP analogs, e) adenine nucleotides, and f) amino acids. These protective devices will be applied to both whole animal preparations and isolated tubule preparations.